Dittmer D, Pati S, Zambetti G, Chu S, Teresky A K, Moore M, Finlay C, Levine A J
Department of Molecular Biology, Princeton University, New Jersey 08544-1014.
Nat Genet. 1993 May;4(1):42-6. doi: 10.1038/ng0593-42.
We report that the expression of murine or human mutant p53 proteins in cells with no endogenous p53 proteins confers new or additional phenotypes upon these cells. Mutant p53 proteins expressed in cell lines lacking p53 resulted in either enhanced tumorigenic potential in nude mice ((10)3 cells) or enhanced plating efficiency in agar cell culture (human SAOS-2 cells). Also, mutant human p53 alleles, unlike the wild-type p53 protein, could also enhance the expression of a test gene regulated by the multi-drug resistance enhancer-promoter element. These data demonstrate a gain of function associated with p53 mutations in addition to the loss of function shown previously to be associated with mutations in this tumour suppressor gene.
我们报告称，在没有内源性p53蛋白的细胞中表达鼠类或人类突变型p53蛋白会赋予这些细胞新的或额外的表型。在缺乏p53的细胞系中表达的突变型p53蛋白，在裸鼠中（(10)3个细胞）会导致致瘤潜能增强，或者在琼脂细胞培养中（人类SAOS-2细胞）会提高平板接种效率。此外，与野生型p53蛋白不同，突变型人类p53等位基因还可以增强由多药耐药增强子-启动子元件调控的测试基因的表达。这些数据表明，除了先前显示与该肿瘤抑制基因突变相关的功能丧失外，p53突变还与功能获得有关。
